The invention is directed to a process for the separation of L-leucine and L-isoleucine in aminoacid mixtures (i.e. aminocarboxylic acid mixtures) which contain 30 to 65 weight percent L-leucine, 35 to 70 weight percent L-isoleucine, and at most 35 weight percent of other aminoacids, in each case based on the dry material.
The aminoacids leucine and isoleucine have the same empirical formula C.sub.6 H.sub.13 NO.sub.2 and differ only through the structure of the branched aliphatic side chain R: ##STR1##
Because of their very similar structural characteristics these aminoacids show very similar properties in their physical and chemical behavior and their separation presents great difficulties.
The first separation of leucine and isoleucine was carried out via the copper complexes. In that case the dried copper complexes of the aminoacids were extracted with methanol, the copper salt of isoleucine thereby dissolves. In a similar process the cobalt complexes of the aminoacids were also separated by extraction with alcohol. However, with these processes there arises the problem of the recovery of the metals and the further purification of the aminoacids.
Other authors described the separation of leucine and isoleucine with aromatic sulfonic acids. Thus there were proposed the use of 2-bromotoluene-5-sulfonic acid or naphthalene-2-sulfonic acid for the precipitation of leucine and 1-chloro-4-naphthalene-sulfonic acid or 2-naphthol-6-sulfonic acid for the precipitation of isoleucine. Benzenesulfonic acid as well as p-toluenesulfonic acid were also employed for the separation of leucine and isoleucine. In these processes the precipitate must be purified by numerous recrystallizations and a particular problem is created by the separation of the precipitation agent which is frequently strongly toxic.
In a further known process mixtures of isoleucine, leucine and valine are separated through a multistep crystallization of L-leucine in the pH range 1.5 to 2.0 and subsequently L-isoleucine hydrochloride is obtained by crystallization from concentrated hydrochloric acid, in which case the mother liquor becomes enriched with residual leucine. However, according to this process, there cannot be obtained 1-leucine in sufficient purity for pharmaceutical uses.